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Hepatocellular-Targeted mRNA Delivery Using Functionalized Selenium Nanoparticles In Vitro.

Dhireshan Singh1, Moganavelli Singh1

  • 1Nano-Gene and Drug Delivery Group, Discipline of Biochemistry, University of KwaZulu-Natal, Private Bag X54001, Durban, South Africa.

Pharmaceutics
|March 6, 2021
PubMed
Summary
This summary is machine-generated.

Selenium nanoparticles (SeNPs) show promise as gene delivery vehicles. Functionalized SeNPs efficiently delivered FLuc-mRNA to liver cancer cells, demonstrating targeted gene expression with low toxicity.

Keywords:
FLuc-mRNASelenium nanoparticleschitosangene expressionhepatocellular carcinomalactobionic acidtargeting

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Area of Science:

  • Nanomedicine
  • Biotechnology
  • Materials Science

Background:

  • Selenium nanoparticles (SeNPs) offer enhanced bioavailability and reduced toxicity compared to selenium.
  • Gene delivery systems are crucial for targeted cancer therapy.
  • Hepatocellular carcinoma (HCC) presents a significant therapeutic challenge, necessitating novel delivery strategies.

Purpose of the Study:

  • To formulate functionalized SeNPs for targeted delivery of FLuc-mRNA to hepatocellular carcinoma (HepG2) cells.
  • To evaluate the binding, protection, and delivery efficiency of SeNPs with mRNA.
  • To assess the in vitro cytotoxicity and targeted gene expression of the developed nanocarriers.

Main Methods:

  • SeNPs were synthesized and functionalized with chitosan, polyethylene glycol, and lactobionic acid for ASGPR targeting.
  • Nanoparticle characterization included FTIR, UV-vis spectroscopy, TEM, and NTA.
  • mRNA binding, protection assays, MTT cytotoxicity assay, and luciferase reporter gene assay were performed.

Main Results:

  • Functionalized SeNPs were spherical, with sizes ranging from 57.2-130.0 nm and zeta potentials of 14.9-31.4 mV.
  • SeNP-mRNA complexes demonstrated efficient binding, compaction, and protection against nuclease degradation.
  • Targeted gene expression was significantly higher in HepG2 cells treated with lactobionic acid-functionalized SeNPs, with negligible cytotoxicity.

Conclusions:

  • Functionalized SeNPs are effective nanocarriers for nucleic acid delivery.
  • Lactobionic acid-functionalized SeNPs show potential for targeted gene delivery to hepatocellular carcinoma cells.
  • These findings support further investigation of SeNPs in advanced gene therapy applications.